Search

Limitations of vitamin K antagonists as chronic oral anticoagulant therapy have largely been supplanted by direct factor IIa and factor Xa inhibitor oral anticoagulants with similar efficacy but an overall better safety profile, lack of routine monitoring, and very limited drug–drug interactions compared with agents such as warfarin. However, an increased risk of bleeding remains even with these new-generation oral anticoagulants in fragile patient populations, in patients requiring dual or triple antithrombotic therapy, or high bleed risk surgeries. Epidemiologic data in patients with hereditary factor XI deficiency and preclinical studies support the notion that factor XIa inhibitors have the ability to be an effective but potentially safer alternative to existing anticoagulants, based on their ability to prevent thrombosis directly within the intrinsic pathway without affecting hemostatic mechanisms. As such, various types of factor XIa inhibitors have been studied in early phase clinical studies, including inhibitors of the biosynthesis of factor XIa with antisense oligonucleotides or direct inhibitors of factor XIa using small peptidomimetic molecules, monoclonal antibodies, aptamers, or natural inhibitors. In this review, we discuss how different types of factor XIa inhibitors work and present findings from recently published Phase II clinical trials across multiple indications, including stroke prevention in atrial fibrillation, dual pathway inhibition with concurrent antiplatelets post–myocardial infarction, and thromboprophylaxis of orthopaedic surgery patients. Finally, we refer to ongoing Phase III clinical trials of factor XIa inhibitors and their potential to provide definitive answers regarding their safety and efficacy in preventing thromboembolic events in specific patient groups.

Background Coronavirus disease 2019 (COVID-19) is associated with venous and arterial thromboembolism (VTE and ATE) and all-cause mortality (ACM) in hospitalized patients. High-quality data are needed on post-discharge outcomes in patients with cardiovascular disease. Objectives To analyze outcomes and identify risk factors for ATE, VTE, and ACM in a high-risk subgroup of hospitalized COVID-19 patients with baseline cardiovascular disease. Methods We investigated post-discharge rates and associated risk factors of ATE, VTE, and ACM in 608 hospitalized COVID-19 patients with coronary artery disease (CAD), carotid artery stenosis (CAS), peripheral arterial disease (PAD), or ischemic stroke. Results Through 90 days post-discharge, outcome rates were: ATE 27.3% (10.2% myocardial infarction, 10.1% ischemic stroke, 13.2% systemic embolism, 12.7% major adverse limb event); VTE 6.9% (4.1% deep vein thrombosis, 3.6% pulmonary embolism); composite of ATE, VTE, or ACM 35.2% (214/608). Multivariate analysis showed significant association between this composite endpoint and age > 75 years (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.22-2.94, p = 0.004), PAD (OR: 3.23, 95% CI: 1.80-5.81, p = < 0.0001), CAS (OR: 1.74, 95% CI: 1.11-2.75, p = 0.017), congestive heart failure (CHF) (OR: 1.84, 95% CI: 1.02-3.35, p = 0.044), previous VTE (OR: 3.08, 95% CI: 1.75-5.42, p < 0.0001), and intensive care unit (ICU) admission (OR: 2.93, 95% CI: 1.81-4.75, p < 0.0001). Conclusions COVID-19 inpatients with cardiovascular disease experience high rates of ATE, VTE, or ACM through 90 days post-discharge. Age > 75 years, PAD, CAS, CHF, previous VTE, and ICU admission are independent risk factors.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15–30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.

Background We aimed to identify the prevalence and predictors of venous thromboembolism (VTE) or mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. Methods A retrospective cohort study of hospitalized adult patients admitted to an integrated health care network in the New York metropolitan region between March 1, 2020 and April 27, 2020. The final analysis included 9,407 patients with an overall VTE rate of 2.9% (2.4% in the medical ward and 4.9% in the intensive care unit [ICU]) and a VTE or mortality rate of 26.1%. Most patients received prophylactic-dose thromboprophylaxis. Multivariable analysis showed significantly reduced VTE or mortality with Black race, history of hypertension, angiotensin converting enzyme/angiotensin receptor blocker use, and initial prophylactic anticoagulation. It also showed significantly increased VTE or mortality with age 60 years or greater, Charlson Comorbidity Index (CCI) of 3 or greater, patients on Medicare, history of heart failure, history of cerebrovascular disease, body mass index greater than 35, steroid use, antirheumatologic medication use, hydroxychloroquine use, maximum D-dimer four times or greater than the upper limit of normal (ULN), ICU level of care, increasing creatinine, and decreasing platelet counts. Conclusion In our large cohort of hospitalized COVID-19 patients, the overall in-hospital VTE rate was 2.9% (4.9% in the ICU) and a VTE or mortality rate of 26.1%. Key predictors of VTE or mortality included advanced age, increasing CCI, history of cardiovascular disease, ICU level of care, and elevated maximum D-dimer with a cutoff at least four times the ULN. Use of prophylactic-dose anticoagulation but not treatment-dose anticoagulation was associated with reduced VTE or mortality.

Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher's exact tests were used for testing the null hypothesis of independence between the clinical outcome and patient characteristic, where the test p-values were reported. Results There were 3,007 patients with atrial fibrillation requiring perioperative DOAC management. There was no significant difference in bleeding or thromboembolic outcomes according to DOAC type/dose regimen, renal function, or patient age. The rate of MB was significantly higher with high bleed risk procedures than low bleed risk procedures in apixaban-treated patients (2.9 vs. 0.59%; p Conclusion Our results suggest that in DOAC-treated patients who received standardized perioperative management, surgical bleed risk is an important determinant of bleeding but not thromboembolic outcomes, although this finding was not consistent across all DOACs. There were no differences in bleeding and thromboembolism according to DOAC type and dose, renal function, or age.

Venous thromboembolism (VTE) remains a major cause of morbidity and mortality in hospitalized medically ill patients. These patients constitute a heterogeneous population, whose VTE risk is dependent upon the acute medical illness, immobility status, and patient-specific risk factors that have been incorporated into individualized VTE risk assessment models. Randomized placebo-controlled trials (RCTs) have shown both efficacy and net clinical benefit of in-hospital thromboprophylaxis, which is supported by guideline recommendations. The data for extended posthospital discharge thromboprophylaxis are more nuanced. RCTs comparing standardized duration low-molecular weight heparin versus extended duration direct oral anticoagulants, such as betrixaban and rivaroxaban, have shown efficacy and net clinical benefit in select groups of high VTE and low-bleed risk populations of hospitalized medically ill patients. These oral agents are now approved for both in-hospital and extended thromboprophylaxis. However, the most recent guidelines do not recommend routine use of these agents for extended thromboprophylaxis. Longitudinal studies in medically ill patients have shown that the majority of VTE events occur in the posthospital discharge setting within 6 weeks of hospitalization. This, coupled with the short hospital length-of-stay and lack of routine postdischarge thromboprophylaxis in U.S. health care settings, has dampened quality improvement efforts aimed at reducing hospital-acquired VTE. The aim of this multidisciplinary document is to provide an evidence-based framework to guide clinicians in assessing VTE and bleeding risk in hospitalized medically ill patients using an individualized, risk-adapted, and patient-centered approach, with the aim of providing clinical pathways toward the use of appropriate type and duration of available thromboprophylactic agents.

Background The IMPROVE score is a validated venous thromboembolism (VTE) assessment tool to risk stratify hospitalized, medically ill patients based on clinical variables. It was hypothesized that addition of D-dimer measurement to derive a new IMPROVEDD score would improve identification of at risk of VTE. Methods The association of the IMPROVE score and D-dimer ≥ 2 × the upper limit of normal (ULN) with the risk of symptomatic deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was evaluated in 7,441 hospitalized, medically ill patients randomized in the APEX trial. Based on the Cox regression analysis, the IMPROVEDD score was derived by adding two points to the IMPROVE score if the D-dimer was ≥ 2 × ULN. Results Baseline D-dimer was independently associated with symptomatic VTE through 77 days (adjusted HR: 2.22 [95% CI: 1.38–1.58], p = 0.001). Incorporation of D-dimer into the IMPROVE score improved VTE risk discrimination (ΔAUC: 0.06 [95% CI: 0.02–0.09], p = 0.0006) and reclassification (continuous NRI: 0.34 [95% CI: 0.17–0.51], p = 0.001; categorical NRI: 0.13 [95% CI: 0.03–0.23], p = 0.0159). Patients with an IMPROVEDD score of ≥2 had a greater VTE risk compared with those with an IMPROVEDD score of 0 to 1 (HR: 2.73 [95% CI: 1.52–4.90], p = 0.0007). Conclusion Incorporation of D-dimer into the IMPROVE VTE risk assessment model further improves risk stratification in hospitalized, medically ill patients who received thromboprophylaxis. An IMPROVEDD score of ≥2 identifies hospitalized, medically ill patients with a heightened risk for VTE through 77 days.

SummaryAcutelly-ill hospitalised medical patients are at risk of venous thromboembolism (VTE), both in-hospital and in the immediate post-discharge period, and mortality from VTE is thought to be particularly high in this patient population. However, despite previous mandates from international antithrombotic guidelines such as those of the American College of Chest Physicians (ACCP) for the “universal” use of thromboprophylaxis in hospitalised medical patients, global audits suggest that implementation of thromboprophylaxis continues to be challenging because of the perceived higher risk of bleeding and lower risk of VTE than that reported in clinical trials. Recent population-based studies also reveal that a “universal” hospital-only thromboprophylactic strategy does not reduce the community burden of VTE from this population, which may constitute nearly one quarter of the attributable risk of VTE. Lastly, four large randomised placebo-controlled trials of extended thromboprophylaxis have failed to show a definitive net clinical benefit in hospitalised medical patients. Recent large-scale efforts in deriving and validating scored VTE and bleed risk assessment models (RAMs) have been completed in the medically-ill population. In addition, an elevated D-dimer as a new biomarker to identify at-VTE risk medically ill patients has also undergone prospective evaluation. This paper will review current concepts of VTE and bleed risk in hospitalised medical patients, both in the hospital as well as the post-hospital discharge period, and will discuss new paradigms of thromboprophylaxis in this population using an individualised, patient-centered approach.

SummaryAnnual costs for venous thromboembolism (VTE) have been defined within the United States (US) demonstrating a large opportunity for cost savings. Costs for the European Union-28 (EU-28) have never been defined. A literature search was conducted to evaluate EU-28 cost sources. Median costs were defined for each cost input and costs were inflated to 2014 Euros (€) in the study country and adjusted for Purchasing Power Parity between EU countries. Adjusted costs were used to populate previously published cost-models based on adult incidence-based events. In the base model, annual expenditures for total, hospital-associated, preventable, and indirect costs were €1.5–2.2 billion, €1.0–1.5 billion, €0.5–1.1 billion and €0.2–0.3 billion, respectively (indirect costs: 12 % of expenditures). In the long-term attack rate model, total, hospital-associated, preventable, and indirect costs were €1.8–3.3 billion, €1.2–2.4 billion, €0.6–1.8 billion and €0.2–0.7 billion (indirect costs: 13 % of expenditures). In the multiway sensitivity analysis, annual expenditures for total, hospital-associated, preventable, and indirect costs were €3.0–8.5 billion, €2.2–6.2 billion, €1.1–4.6 billion and €0.5–1.4 billion (indirect costs: 22 % of expenditures). When the value of a premature life-lost increased slightly, aggregate costs rose considerably since these costs are higher than the direct medical costs. When evaluating the models aggregately for costs, the results suggests total, hospital-associated, preventable, and indirect costs ranging from €1.5–13.2 billion, €1.0–9.7 billion, €0.5–7.3 billion and €0.2–6.1 billion, respectively. Our study demonstrates that VTE costs have a large financial impact upon the EU-28’s healthcare systems and that significant savings could be realised if better preventive measures are applied.

SummaryIn patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain. We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders. Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p < 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs 1.8 %, p < 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p < 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/ procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.

In the Original Article by Douketis et al. "The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant who Need an Elective Surgery or Procedure: Design and Rationale (Thromb Haemost 2017;117:2415-2424; DOI: 10.1160/TH17-08-0553), the authors have identified two errors that they wish to correct: First, on page 2419, second paragraph, Clinical Outcomes subheading, the authors state that, "The primary clinical outcomes are arterial thromboembolism, comprising stroke (ischemic or haemorrhagic), systemic embolism or transient ischemic attack and major bleeding. The inclusion of "haemorrhagic stroke is incorrect as only ischemic strokes are included in their definition of an arterial thromboembolism outcome. The definitions of study outcomes are correctly indicated in Appendix A (pg. 2424) of the paper, where the authors state: "The second primary outcome is arterial thromboembolism, comprising (1) ischemic stroke, defined as any new focal neurologic deficit that persists for 24 hours or any new focal neurologic deficit of any duration that occurs with evidence of acute infarction on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain; (2) systemic embolism, defined as symptomatic embolism to upper or lower extremity or abdominal organ, confirmed intraoperatively or by objective imaging studies (e.g. CT angiography) and (3) transient ischemic attack, defined as symptomatic focal neurologic deficit (lasting typically 1 hour) that occurs with no evidence of acute infarction on CT/MRI of the brain. Second, the depiction of the pre-procedure interruption interval for dabigatran-treated patientswith a CrCl 50 mL/min is incorrect in Figure 1 (pg. 2418) of the paper, as the arrow should extend so it reflects 2 days off treatment (i.e., day -2 and day -1). The incorrect (currently published) version is shown below, with incorrect area shaded in red: (Figure Presented).

SummaryLimited evidence exists to guide the use of early parenteral anticoagulation following mechanical heart valve replacement (MVR). The purpose of this study was to compare the 30-day rates of thrombotic and bleeding complications for MVR patients receiving therapeutic versus prophylactic dose bridging regimens. In this retrospective cohort study we reviewed anticoagulation management and outcomes of all patients undergoing MVR at five Canadian hospitals between 2003 and 2010. The primary efficacy outcome was thromboembolism (stroke, transient ischaemic attack, systemic embolism or valve thrombosis) and the primary safety outcome was major bleeding at 30-days. Outcomes were compared using a logistic regression model adjusting for propensity score and in a 1:1 propensity matched sample. A total of 1777 patients underwent mechanical valve replacement, of whom 923 received therapeutic dose bridging anticoagulation and 764 received prophylactic dose bridging postoperatively. Sixteen patients (1.8 %) who received therapeutic dose bridging and fifteen patients (2.1 %) who received prophylactic dose bridging experienced the primary efficacy outcome (odds ratio [OR] 0.90; 95 % confidence interval [CI], 0.37 to 2.18, p=0.81). Forty-eight patients (5.4 %) in the therapeutic dosing group and 14 patients (1.9 %) in the prophylactic dosing group experienced the primary safety outcome of major bleeding (OR 3.23; 95 % CI, 1.58 to 6.62; p=0.001). The direction of the effects, their magnitude and significance were maintained in the propensity matched analysis. In conclusion, we found that early after mechanical valve replacement, therapeutic dose bridging was associated with a similar risk of thromboembolic complications, but a 2.5 to 3-fold increased risk of major bleeding compared with prophylactic dose bridging.

SummaryAnticoagulation therapy for the prevention of venous thromboembolic events is indicated in patients after major orthopaedic surgery and in hospitalised acutely ill medical patients, who have a high or moderate risk of venous thromboembolism (VTE), respectively. Clinical trials have clearly demonstrated that short-term anticoagulation reduces the risk of VTE in these patient groups and that longer-term anticoagulation is beneficial for some indications. Evidence-based guidelines for throm-boprophylaxis have been developed based on these studies. However, despite these guidelines, thromboprophylaxis is still underused, or used suboptimally, in many patients. This is, in part, because of the limitations of traditional anticoagulants such as unfractionated heparin, lowmolecular-weight heparin, synthetic pentasaccharides, and vitamin K antagonists. Newer oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran etexilate, have certain advantages over traditional agents. They can be administered orally at a fixed dose without routine coagulation monitoring and have minimal food and drug interactions. These characteristics may result in better adherence to guidelines and improved patient outcomes. This review provides an overview of phase III clinical trial data for these newer anticoagulants in major orthopaedic surgery and in hospitalised acutely ill medical patients, and discusses their potential for extended use in the post-hospital discharge setting. All three newer oral anticoagulants are approved in many countries for the prevention of VTE after hip replacement or knee replacement surgery in adult patients, and it is likely that these drugs will contribute considerably towards reducing the substantial healthcare burden associated with VTE.

SummaryPreventable venous thromboembolism (VTE) and “appropriate” type, dose, and duration of prophylaxis are emerging concepts. Contemporary definitions by key quality organisations, including the World Health Organization, have shifted towards “preventable” VTE being considered an adverse event or adverse drug event. A decision tree and cost model were developed to estimate the United States health care costs for total deep-vein thrombosis (DVT), total hospital-acquired DVT, and total “preventable” DVT. Annual cost ranges were obtained in 2010 US dollars for total ($7.5 to $39.5 billion), hospital-acquired ($5 to $26.5billion), and preventable ($2.5 to $19.5 billion) DVT costs. When the sensitivity analysis was applied – taking into consideration higher incidence rates and costs – annual US total, hospital-acquired, and “preventable” DVT costs ranged from $9.8 to $52 billion, $6.8 to $36 billion, and $3.4 to $27 billion, respectively.

SummaryLimited data are available regarding the risk for venous thromboembolism (VTE) and VTE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VTE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VTE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active non-infectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40–45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VTE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VTE risk and providing prophylaxis to hospitalised medical patients.

Reconstruction of total nasal defects remains one of the most difficult problems in plastic surgery as the nose combines aesthetics and function. Standard techniques using either forehead or nasolabial flaps do not have a place in the case of extensive scarring on the face or areas with high risk of cancer recurrence on the face. In these cases, microsurgical free tissue transfer for the soft tissue reconstruction in combination with bone grafts or implants for the nasal skeleton are ideal. We report the use of prelaminated radial forearm flap with porous polyethylene implants for total nasal reconstruction.

Patients with clinical conditions such as surgery, trauma, and acute medical illness have a transiently increased risk of venous thromboembolism and merit consideration for adequate thromboprophylaxis. The choice of an appropriate pharmacologic or physical means of prophylaxis should be made taking into account both the thrombotic and bleeding risk associated with patient-related factors and the type of surgery or other disease state involved. A large number of randomized clinical trials, meta-analyses, and guidelines developed by scientific societies worldwide have addressed this issue and have provided information and recommendations that should be considered carefully. The aim of this review is to provide the practicing physician with a brief updated summary of the subject, stratifying those patients at low thrombotic risk who do not require specific thromboprophylaxis apart from early ambulation, from those at moderate or higher thrombotic risk. Patients at moderate thrombotic risk face a 10 to 20% risk of deep vein thrombosis (DVT) and require prophylaxis with low-dose unfractionated heparin or low molecular weight heparins (LMWHs) at a dosage3400 U once daily, or with graduated elastic stockings if their bleeding risk is high. Patients with an expected 20 to 40% DVT rate without prophylaxis are considered at high thrombotic risk and should be treated preferentially with LMWHs at high prophylactic dosage (3400 U). Patients undergoing major orthopedic surgery face a DVT rate40%, are considered at very high risk of venous thromboembolism, and should be given either LMWHs at high prophylactic dosage, fondaparinux, or vitamin K antagonists--either alone or in association with intermittent pneumatic compression devices.

SummaryHospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10–30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk o f VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.